Epigenomic Reordering Induced by Polycomb Loss Drives Oncogenesis but Leads to Therapeutic Vulnerabilities in Malignant Peripheral Nerve Sheath Tumors.

ABSTRACT: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with recurrent loss-of-function alterations in polycomb-repressive complex 2 (PRC2), a histone-modifying complex involved in transcriptional silencing. To understand the role of PRC2 loss in pathogenesis and identify therapeutic targets, we conducted parallel global epigenomic and proteomic analysis of archival formalin-fixed, paraffin-embedded (FFPE) human MPNST with and without PRC2 loss (MPNST_LOSS vs. MPNST_RET). Loss of PRC2 resulted in increased histone posttranslational modifications (PTM) associated with active transcription, most notably H3K27Ac and H3K36me2, whereas repressive H3K27 di- and trimethylation (H3K27me2/3) marks were globally lost without a compensatory gain in other repressiv

SUBMITTER: Wojcik JB 

PROVIDER: S-EPMC6637743 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature